Nonomuraea corallina sp. nov., isolated from coastal sediment in Samila Beach, Thailand: insights into secondary metabolite synthesis as anticancer potential

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 20, 2023

A novel marine actinomycete, designated strain MCN248 T , was isolated from the coastal sediment in Songkhla Province, Thailand. Based on 16S rRNA gene sequences, new isolate closely related to Nonomuraea harbinensis DSM45887 (99.2%) and ferruginea DSM43553 (98.6%). Phylogenetic analyzes based sequences showed that clustered with . However, digital DNA–DNA hybridization presented a low relatedness of 40.2% between above strains. This contained meso-diaminopimelic acid. The acyl type peptidoglycan acetyl, mycolic acids were absent. major menaquinones MK-9(H 2 ) 4 ). whole cell sugars consisted madurose, ribose, mannose, glucose. Diphosphatidylglycerol, hydroxyl-phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol detected as phospholipids. predominant cellular fatty iso -C 16:0 (40.4%), 10-methyl-C 17:0 (22.1%), C 17:1 ω 8c (10.9%). DNA G + content genomic 71.7%. With silico analyzes, antiSMASH platform uncovered diverse 29 secondary metabolite biosynthesis arsenal, including non-ribosomal peptide synthetase (NRPS) polyketide synthase (PKS) high prevalence cluster encoding pathways for production anticancer cytotoxic compounds. Consistently, crude extract could inhibit colorectal HCT-116 cancer cells at final concentration 50 μg/mL. polyphasic approach, species genus which name corallina sp. nov. is proposed. (=NBRC115966 = TBRC17110

Language: Английский

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Pyrvinium Pamoate Enhances the Anti-cancer Activities of Gemcitabine in Pancreatic Cancer

Published: Feb. 29, 2024

Pancreatic cancer is an intractable disease with the worst prognosis of all cancers. The currently used treatment regimens do not significantly impact patient survival, and therefore, effective strategies are urgently needed. Drug repurposing, which identifies new indications for existing approved drugs, has proven to be a promising approach anti-cancer drug discovery. Indeed antihelmintic drug, pyrvinium pamoate shown promise as anti-pancreatic but date, inhibition mitochondrial function only mechanism action described in pancreatic cancer. This study showed, using 2D cell cultures 3D spheroids, that exhibited short- long-term cytotoxicity, inhibited epithelial-to-mesenchymal transition invasion migration. Mechanistically, induced DNA damage, PI3K/AKT survival pathway, triggered cycle arrests, well apoptotic autophagic death. Importantly, acted synergistically first-line gemcitabine culture models. provided evidence single agent combination

Language: Английский

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Rapidly-manufactured CD276 CAR-T cells exhibit enhanced persistence and efficacy in pancreatic cancer

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 8, 2024

Abstract Background Pancreatic cancer is one of the most lethal malignancies and lack treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized made great breakthroughs in treating hematological malignancies, however its success solid cancers remains limited mainly due to tumor-specific antigens. On other hand, prolonged traditional manufacturing process poses challenges, taking 2 6 weeks impacting patient outcomes. CD276 recently emerged as a potential therapeutic target for anti-solid therapy. Here, we investigated efficacy CAR-T rapidly-manufactured against pancreatic cancer. Methods In present study, was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge transmembrane domain, 4-1BB CD3ζ intracellular domains. Additionally, (named Dash CAR-T) innovatively developed shortening duration ex vitro culture reduce time. We evaluated anti-tumor further compared functional assessment conventional vivo detecting immunophenotypes, killing ability, expansion capacity tumor-eradicating effect CAR-T. Results found that strongly expressed multiple cell lines could efficiently kill these cells. Moreover, successfully manufactured within 48–72 h validation carried out subsequently. vitro, possessed less-differentiated phenotype robust proliferative ability xenograft mouse model, showed enhanced anti-pancreatic T expansion. Besides, except high-dose group, body weight mice maintained stable, state normal. Conclusions this proved exhibited powerful activity cells vivo. More importantly, demonstrated feasibility, acceptable safety superior generated with reduced The results above studies indicated might be novel promising strategy treatment.

Language: Английский

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Eficácia e toxicidade dos regimes quimioterápicos no tratamento do Câncer Pancreático metastático

Caderno Pedagógico, Journal Year: 2024, Volume and Issue: 21(8), P. e6995 - e6995

Published: Aug. 23, 2024

Em 2020, o câncer de pâncreas resultou em aproximadamente 495.773 novos casos e 466.003 mortes relacionadas à doença todo mundo. Além da opção cirúrgica, tratamento do pancreático abrange uso quimioterápicos, como regime FOLFIRINOX, que combina fluorouracil, leucovorina, irinotecano oxaliplatina. Outras abordagens incluem paclitaxel ligado albumina conjunto com gemcitabina nanoliposomal associado a leucovorina fluorouracil. O objetivo é fornecer uma visão atualizada possa guiar decisões terapêuticas mais informadas, ênfase na individualização tratamento, visando maximizar os benefícios clínicos para população pacientes diversificada. Esta revisão literatura foi conduzida avaliar eficácia toxicidade dos regimes quimioterápicos utilizados no metastático. A seguiu abordagem utilizando descritores booleanos arantir abrangência precisão seleção estudos. Os estudos destacados Tabelas revelaram apesar sua elevada eficácia, está considerável, limita aplicabilidade estado geral debilitado. Entretanto, integração protocolo FOLFIRINOX são essenciais melhorar tempo vida qualidade desta neoplasia desfechos pacientes. personalização considerando as características individuais inclusão cuidados multidisciplinares, mostrou-se essencial otimizar resultados vida.

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Discovery of novel TANK-Binding Kinase 1 (TBK1) inhibitor against pancreatic ductal adenocarcinoma

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 283, P. 137296 - 137296

Published: Nov. 6, 2024

Language: Английский

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